Some 250 years after the systematic experiments by Musschenbroek and their rationalization by Euler, for the first time we show that it is possible to design structures (i.e. mechanical systems whose elements are governed by the equation of the elastica) exhibiting bifurcation and instability ('buckling') under tensile load of constant direction and point of application ('dead'). We show both theoretically and experimentally that the behaviour is possible in elementary structures with a single degree of freedom and in more complex mechanical systems, as related to the presence of a structural junction, called 'slider', allowing only relative transversal displacement between the connected elements. In continuous systems where the slider connects two elastic thin rods, bifurcation occurs both in tension and in compression, and is governed by the equation of the elastica, employed here for tensile loading, so that the deformed rods take the form of the capillary curve in a liquid, which is in fact governed by the equation of the elastica under tension. Since axial load in structural elements deeply influences dynamics, our results may provide application to innovative actuators for mechanical wave control; moreover, they open a new perspective in the understanding of failure within structural elements.
Background In the last decades, the relationship between social networking sites (SNSs) and older people’s loneliness is gaining specific relevance. Studies in this field are often based on qualitative methods to study in-depth self-perceived issues, including loneliness and well-being, or quantitative surveys to report the links between information and communication technologies (ICTs) and older people’s well-being or loneliness. However, these nonexperimental methods are unable to deeply analyze the causal relationship. Moreover, the research on older people’s SNS use is still scant, especially regarding its impact on health and well-being. In recent years, the existing review studies have separately focused their attention on loneliness and social isolation of older people or on the use of ICTs and SNSs in elderly populations without addressing the relationship between the former and the latter. This thorough qualitative review provides an analysis of research performed using an experimental or quasi-experimental design that investigates the causal effect of ICT and SNS use on elderly people’s well-being related to loneliness. Objective The aims of this review are to contrast and compare research designs (sampling and recruitment, evaluation tools, interventions) and the findings of these studies and highlight their limitations. Methods Using an approach that integrates the methodological framework for scoping studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews, we identified 11 articles that met our inclusion criteria. A thematic and content analysis was performed based on the ex post categorization of the data on the selected studies, and the data were summarized in tables. Results The analysis of the selected articles showed that: (1) ICT use is positively but weakly related to the different measures of older people’s well-being and loneliness, (2) overall, the studies under review lack a sound experimental design, (3) the main limitations of these studies lie in the lack of rigor in the sampling method and in the recruitment strategy. Conclusions The analysis of the reviewed studies confirms the existence of a beneficial effect of ICT use on the well-being of older people in terms of reduced loneliness. However, the causal relationship is often found to be weak. This review highlights the need to study these issues further with adequate methodological rigor.
The results of this study suggest that the cardiovascular response to exercise training may be different in men and women. Women may benefit more from interventions aimed to increase physical activity as a tool for prevention of cardiovascular morbidity and mortality.
Bifurcation of an elastic structure crucially depends on the curvature of the constraints against which the ends of the structure are prescribed to move, an effect that deserves more attention than it has received so far. In fact, we show theoretically and provide definitive experimental verification that an appropriate curvature of the constraint over which the end of a structure has to slide strongly affects buckling loads and can induce: (i) tensile buckling; (ii) decreasing-(softening), increasing-(hardening) or constant-load (null stiffness) postcritical behaviour; and (iii) multiple bifurcations, determining for instance two bifurcation loads (one tensile and one compressive) in a single-degreeof-freedom elastic system. We show how to design a constraint profile to obtain a desired postcritical behaviour and we provide the solution for the elastica constrained to slide along a circle on one end, representing the first example of an inflexional elastica developed from a buckling in tension. These results have important practical implications in the design of compliant mechanisms and may find applications in devices operating in quasi-static or dynamic conditions, even at the nanoscale.
Background: Preventing dementia onset is one of the global public health priorities: around 35% of dementia cases could be attributable to modifiable risk factors. These estimates relied on secondary data and did not consider the concurrent effect of non-modifiable factors and death. Here, we aimed to estimate the potential reduction of dementia incidence due to modifiable risk factors elimination, controlling for non-modifiable risk factors and for the competing risk of death. Methods: Participants from the InveCe.Ab population-based prospective cohort (Abbiategrasso, Italy) without a baseline dementia diagnosis and attending at least one follow-up visit were included (N = 1100). Participants underwent multidimensional assessment at baseline and after 2, 4, and 8 years, from November 2009 to January 2019. Modifiable risk factors were low education, obesity, hypertension, diabetes, depression, smoking, physical inactivity, hearing loss, loneliness, heart disease, stroke, head injury, and delirium. Non-modifiable risk factors were age, sex, and APOE ε4 genotype. The primary endpoint was dementia diagnosis within the follow-up period (DSM-IV criteria). We performed competing risk regression models to obtain sub-hazard ratio (SHR) for each exposure, with death as competing risk. The exposures associated with dementia were included in a multivariable model to estimate their independent influence on dementia and the corresponding population attributable fraction (PAF). Results: Within the study period (mean follow-up, 82.3 months), 111 participants developed dementia (10.1%). In the multivariable model, APOE ε4 (SHR = 1.89, 95% CI 1.22-2.92, p = 0.005), diabetes (SHR = 1.56, 95% CI 1.00-2.39, p = 0.043), heart disease (SHR = 1.56, 95% CI 1.03-2.36, p = 0.037), stroke (SHR = 2.31, 95% CI 1.35-3.95, p = 0.002), and delirium (SHR = 8.70, 95% CI 3.26-23.24, p < 0.001) were independently associated with increased dementia risk. In the present cohort, around 40% of dementia cases could be attributable to preventable comorbid diseases.
The design of compliant mechanisms is crucial in several technologies and relies on\ud the availability of solutions for nonlinear structural problems. One of these solutions is given and\ud experimentally validated in the present article for a compliant mechanism moving along a smooth\ud curved profile. In particular, a deformable elastic rod is held by two clamps, one at each end. The\ud first clamp is constrained to slide without friction along a curved profile, while the second clamp\ud moves in a straight line transmitting its motion through the elastic rod to the first clamp. For this\ud system it is shown that the clamp sliding on the profile imposes nontrivial boundary conditions\ud (derived via a variational and an asymptotic approach), which strongly influence buckling and\ud nonlinear structural behaviour. Investigation of this behaviour shows that a compliant mechanism\ud can be designed, which gives an almost neutral response in compression. This behavior could\ud easily be exploited to make a force limiting device. Finally a proof-of-concept device was\ud constructed and tested showing that the analyzed mechanical system can be realized in practice\ud and it behaves tightly to the model, so that it can now be used in the design of machines that\ud use compliant mechanisms
P-glycoprotein (P-gp, MDR1) is a membrane transporter expressed in several regions of our body. It plays a crucial defense role as it mediates the efflux of hundreds of potentially toxic substances. However, P-gp is one of the main causes of failure in cancer chemotherapy, as a number of chemotherapeutic agents are P-gp substrates. Another interesting implication concerns the correlation between P-gp expression impairment and the onset of several central nervous system pathologies such as Alzheimer's and Parkinson's diseases. In view of these considerations, in the present study, a new series of P-gp modulators have been designed, synthesized and evaluated for their activity towards P-gp and two other sister proteins (BCRP and MRP1). The compounds, structurally correlated to the potent but non-selective P-gp inhibitor [4'-(6,7-dimethoxy-3,4-dihydro-1-isoquinolin-2-ylmethyl)biphenyl-4-ol], proved fairly selective towards P-gp, with a potency in the micromolar range. Compounds , and proved capable of restoring doxorubicin toxicity in resistant cancer cells.
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